Sunday, January 25, 2015

Health Benefits of Resveratrol: New Plaudits

Joe: My doctor told me to give up drinking, smoking, and fatty foods.
Sam: What will you do?
Joe: I think I’ll give up my doctor.

I try not to get too excited about memory benefits of supplements, because too often the claims are not substantiated by studies that are well controlled and peer reviewed. I now think resveratrol may be one of the few supplements that benefits brain function.

When I wrote my first blog on research on resveratrol benefits for brain function and memory, there were over 2,000 scientific papers.[1] Don't worry; I am only going to tell you about a few studies.

Resveratrol is an active ingredient in red wine. This compound has been credited for explaining why red-wine drinkers in France, who drink more wine than most people, are healthier than would be predicted by their lifestyle of little exercise and eating lots of cheese. The problem is most studies suggest you would have to drink a 100 or more glasses of red wine a day to get much resveratrol effect (and that effect would obviously be negated by a toxic dose of alcohol). An obviously more healthful choice is the highly concentrated pill forms of resveratrol that are now on the market.

Most of the protective biological actions associated with resveratrol have been associated with its scavenger properties for free radicals and the protective effects that it confers on the heart and diabetes. 

One important study comes from a diabetes research group in Brazil recently who reported a beneficial effect of resveratrol on diabetic rats.[2] Resveratrol (in a modest rat dose of 10 and 20 mg per kilogram per day for 30 days) prevented the impairment of memory induced by diabetes. Resveratrol may be protecting neuron terminals that diabetes can damage. An earlier study by another group showed resveratrol improved glucose metabolism and promoted longevity in diabetic mice.

Another benefit of resveratrol is the anti-oxidant property. The brain produces more free-radical damage than other organs, because it burns so much oxygen. Compared with other organs, the brain has especially low levels of antioxidant defense enzymes. 

One recent study has revealed resveratrol had protective effects against brain damage caused by a chemical that kills acetylcholine neurons. Injection of this toxin into the brain of rats impaired their memory performance in two kinds of maze tasks. The impairment was significantly reduced by repeated injection of resveratrol (10 and 20 mg/kg) per day for 25 days, beginning four days before the toxin injection.[3]

Another recent study examined effects on working memory in mice fed a resveratrol-supplemented diet for four weeks before being injected with a cytokine to induce inflammation and accelerate aging. Resveratrol significantly reduced memory impairment in the aged group, but not in the young adults[4]. The lack of benefit in young adults was a little misleading, in that there was a "ceiling effect" in that the young adults were not impaired by the cytokine injection.

 The practical issue for us is whether resveratrol will help cognitive function in humans, especially healthy humans. It seems likely because other substances that have strong anti-oxidant properties seem to improve memory capability. Because animal studies have shown promise for resveratrol in preventing or treatment several different conditions associated with aging, several human clinical trials have been initiated.[5]

 An impressive new study of older humans, male and female, has just been reported.[6] Twenty-three healthy, but overweight people completed 6 months of daily resveratrol intake (200 mg ― the commercial brand I take has 300 mg/capsule). A paired control group got placebo pills. A double-blind design assured that neither the subjects nor the experimenters knew which individuals were in each group during data processing. Memory tests of word recall revealed significant improvement in the resveratrol group. Resveratrol also increased brain-scan measures of functional connectivity, which identified linked neural activity between the hippocampus and several areas of cerebral cortex.

Because others had shown that resveratrol increased insulin sensitivity in humans, these authors examine several markers important to diabetes. Resveratrol decreased the standing levels of sugar-bound hemoglobin, a standard marker for glucose control.  

What foods besides red grapes have resveratrol? The most likely other sources you would eat or drink are blueberries, cranberries, and peanuts. It is not likely that you could drink or eat enough of such substances to get enough resveratrol to do much good. Because of the scientifically documented benefits of resveratrol, highly concentrated supplements are now on the market (I have been taking it for a couple of years). I haven't given up my two glasses of red wine each day, but I have started taking one of the supplements. I haven't seen any reports that high doses of resveratrol are toxic.

[2] Schmatz R, et al. (2009). Resveratrol prevents memory deficits and the increase in acetylcholinesterase activity in streptozotocin-induced diabetic rats. Eur J Pharmacol. 2009 May 21;610(1-3):42-8. Epub 2009 Mar 19.
[3] Kumar, A. et al. 2007. Neuroprotective effects of resveratrol against intracerebroventricular colchicine-induced cognitive impairment and oxidative stress in rats. Pharmacology.79 (1): 17-26. DOI: 10.1159/000097511
[4] Abraham, J., and Johnson, R. W. 2009. Consuming a diet supplemented with resveratrol reduced infection-related neuroinflammation and deficits in working memory in aged mice. Rejuvenation research. 12 (6): 445-453.  DOI: 10.1089/rej.2009.0888
[5] Smoliga, J. M. et al. (2011). Resveratrol and health – a comprehensive review of human clinical trials.  Mol. Nutrition Food Res. 55: 1129-1141
[6] Witte, A. V., et al. (2014) Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults. J. Neuroscience. 34 23): 7862-7870.

"Memory Medic's latest book is for seniors (Improve Your Memory for a Healthy Brain. Memory Is the Canary in Your Brain's Coal Mine," available in inexpensive e-book format at See also his recent book, "Mental Biology. The New Science of How the Brain and Mind Relate" (Prometheus).

Saturday, January 03, 2015

Happy Thoughts Can Make You More Competent

“Life, liberty, and the pursuit of happiness:” some people might argue that the U.S. Constitution endorses hedonism, and indeed many politicians want to ignore or get rid of the Constitution, but not necessarily because of hedonism. We should not be dismissive about encouraging people to pursue happiness. Happiness can be good for your brain. Depression is surely bad for your brain.

Positive mood states promote more effective thinking and problem solving. A recent scholarly report[1] reviews the literature demonstrating that positive mood broadens the scope of attentiveness, enhances semantic associations over a wider range, improves task shifting, and improves problem-solving capability. The review also documents the changes in brain activation patterns induced by positive mood in subjects while solving problems. Especially important is the dopamine signaling in the prefrontal cortex.

Published studies reveal that a variety of techniques are used to momentarily manipulate mood. These have included making subjects temporarily happy or sad by asking subjects to recall emotionally corresponding past experiences or to view film clips or hear words that trigger happy or sad feelings,

The effect of happiness on broadened attentiveness arises because the brain has better cognitive flexibility and executive control, which in turn makes it easier to be more flexible and creative. Happy problem solvers are better able to select and act upon useful solutions that otherwise never consciously surface. Happiness reduces perseverative tendencies for errant problem-solving strategies. The broadened attentiveness, for example, allows people to attend to more stimuli, both in external visual space and in internal semantic space, which in turn enables more holistic processing. For example, in one cited study, experimenters manipulated subjects’ momentary mood and then measured performance on a task involving matching of visual objects based on their global versus local shapes. Happy moods yielded better global matching.

Other experiments report broader word association performance when subjects are manipulated to be happier. For example, subjects in a neutral mood would typically associate the word “pen” as a writing tool and would associate it with words like pencil or paper. But positive mood subjects would think also of pen as an enclosure and associate it with words like barn or pigs. This effect has been demonstrated with practical effect in physicians, who, when in a happy mood, thought of more disease possibilities in making a differential diagnosis.
The review authors reported their own experiment on beneficial happy mood effects on insightfulness, using a task in which subjects were given three words and asked to think of a fourth word that could be combined into a compound word or phrase. For example, an insightful response to “tooth, potato, and heart” might be “sweet tooth, sweet potato, and sweetheart.” Generating such insight typically requires one to suppress dominant “knee jerk” responses such as associating tooth with pain and recognize that pain does not fit potato while at the same time becoming capable of switching to non-dominant alternatives.

Other cited experiments showed that happy mood improved performance on “Duncker’s candle task.”  Here, subjects are given a box of tacks, a candle, and a book of matches, and are asked to attach a candle to the wall in a way that will burn without dripping wax on the floor. Subjects in a happy mood were more able to realize that the box could be a platform for the candle when the box is tacked to the wall.  

Such effects of happy moods seem to arise from increased neural activity in the prefrontal cortex and cingulate cortex, areas that numerous prior studies have demonstrated as crucial parts of the brain’s executive control network. Similar effects have been observed in EEG studies. Other research suggests that the happiness effect is mediated by increased release of dopamine in the cortex that serves to up-regulate executive control.
The review authors described a meta-analysis of 49 positive-psychology manipulation studies showing that momentary happiness is readily manipulated by such strategies as deliberate optimistic thinking, increased attention to and memory of happy experiences, practicing mindfulness and acceptance, and increasing socialization. The effect occurs in most normal people and even in people with depression, anxiety, and schizophrenia. Biofeedback training, where subjects monitor their own fMRI scans or EEGs, might be an even more effective way for people to train themselves to be happier.

The main point is that people can be as happy as they choose to be.

For more on how positive mood influences memory ability, see my new book, Memory Power 101 ( ). Memory Medic's latest book explores the biology of mind. See "Mental Biology. The New Science of How the Brain and Mind Relate" (Prometheus).

[1] Subramaniam, K. and Vinogradov, S. (2013). Improving the neural mechanisms of cognition through the pursuit of happiness. Frontiers in Human Neuroscience. 7 August. Doi: 10.3389/fnhum.2013.00452